Studies in the Lens and Cataract Biology Section concern the biology of the normal lens and the mechanisms underlying the process of age-related cataractogenesis. The process of isoprenylation in the lens and its possible role in lens development and in cataractogenesis has been a focus of our work during the past year. Isoprenylation, the addition of farnesyl or geranylgeranyl groups to proteins, is required for activity of the Ras superfamily of small GTPases, critical regulators of numerous cellular processes. We have shown that inhibitors of isoprenylation, including the cholesterol-lowering agent lovastatin, can cause cataract in lenses in organ culture. Recently, we have demonstrated that cataract can be prevented in this model system by addition of geranylgeraniol, but not farnesol, to the culture medium. This indicates that one or more proteins that require geranylgeranylation are critical to the initiation of this cataract. Using radiolabeled isoprenoids and the techniques of proteomics, we are working to identify these particular proteins and hopefully the signaling pathways that are involved. A second area of interest in the group concerns the role of pyridine nucleotides in the anti?oxidative defenses of the lens. A catalytic activity that utilizes the reducing equivalents of these compounds to inactivate reactive species of oxygen has been characterized. An enzyme, believed to be responsible for this activity, has been partially purified and mass spectroscopy is currently being used in an attempt to identify it.